Decrease of Vaccine Efficacy against the Delta Variant?

There have been some worrisome headlines recently to the effect that the vaccines are not very effective against the Delta variant of Covid.  Here's one example reporting the "39%" number that Israel has been reporting:  https://www.cnbc.com/2021/07/23/delta-variant-pfizer-covid-vaccine-39percent-effective-in-israel-prevents-severe-illness.html.

I'd like to put my oar in and give an opinion on what I think may be going on.  I'd like to stress that this opinion is less well formed than some of my other opinions, so if anyone has contrary evidence, I'd be happy to hear it so that I can revise what I think.

To explain what I think is happening, first I need to explain some basics--(be warned that this is a dramatic oversimplification):

How immunity works

I think maybe "Immunity" is an unfortunate word, because it has an absolute feel to it: as if whoever is "immune" has an absolute invulnerability to a disease.  This isn't how immunity to disease works, however.  It's important to realize that immunity is the result of specific cellular functions and therefore operates in a specific way that can offer various degrees of protection.

Let's start at the beginning: when a virus first enters the body of an individual who has never before encountered one of its kind.  At this time, it enters a cell, replicates and spreads to other nearby cells.  Fairly soon, it will start to encounter cells that form part of the body's innate immune system--but successful viruses are able to spread an multiply fairly well for a time before triggering a powerful system-wide immune response.  So for a time, the virus is able to spread exponentially from cell to cell without a lot of opposition.

The *timing* is important here: how fast does the body mount an immune response (elevated temperatures, increase immune cell production, etc.), compared to how fast can the virus replicate throughout the body?  In a typical case of first-time Covid, the virus is replicating throughout the body ("incubating") for maybe 3-7 days before the body's defenses really begins noticing things and starts to kick-in with the defense.  This is why Covid can spread so quickly throughout a population--those last few days of non-defended replication can make a person a font of virus particles for other people before they feel ill themselves.

In addition to mounting a systemic immune response, the human body also begins producing a virus-specific response: neutralizing antibodies.  These are tailor-made particles of just the right shape and properties to stick to the invading viruses and de-activate them (mostly, as we know, by gumming up the spike protein and thus preventing the viruses from entering cells in order to replicate).  The initial production of these antibodies, however, takes some time to ramp up--it's something like 7-14 days before we see any of these of note.

Typically, the combination the innate immune system and neutralizing antibodies will be enough to clear the system of the virus before very long.  The person can be sick for some time afterwards (for reasons I'm not clear on and I don't know if anyone *else* is clear on either).  One thing that has been seen for Covid, however, is that people can test positive for Covid for some time after they have been mostly free from symptoms but that these people very rarely spread Covid to other people.  After the body starts producing neutralizing antibodies, those virus particles that are shed by the sick person tend to come out pre-coated with those antibodies--meaning they don't have much capability to infect others.

How immunity continues after illness or vaccination

Once the body has fought off the disease, the innate immunes system settles down.  However, those specific neutralizing antibodies are still produced at a high level for some time--the body remains "alert", as it were, to the presence of the disease.  This doesn't mean that there is some magic shell around the body repelling the virus, however: if another copy of the virus makes it into your nasal mucus membranes, they will again begin to reproduce.  Immunity isn't some chemical property that infuses all of your cells--it's a "herd immunity" of a collection of cells.  So infection will begin to spread again just fine.  The presence of the antibodies, however, means that the infection will not get very far--some cells will be infected, but enough replicated virus particles will become coated with antibodies that the colony of infection will not spread robustly, but rather will die out.

How quickly this happens depends on several factors: how innately good the virus is at spreading, how many antibodies are being produced by the host, and how effective those antibodies are at impeding the growth of the virus.  For some diseases, the antibodies we produce in response to the virus are incredibly effective at stopping the spread of the virus, so that even a small presence of those antibodies are sufficient to very rapidly halt the progression of a viral infection from cell to cell.  The medical field calls immunity to diseases of this sort "sterilizing immunity", because it is as if the body is completely impervious to a disease after getting it.  In reality, there is still some very small level of infection and replication inside the body if the particular virus gets in--it's just that the spread is *so* small that it is not noticeable and produces no relevant results.

With other diseases, however, the neutralizing antibodies are not quite as effective.  And this starts to matter after a while, because the body doesn't keep up production of neutralizing antibodies for a specific disease at a high level, permanently.  It always keeps some around, but it is normal for the levels of these neutralizing antibodies to drop over time.

What the body relies on, after some time has passed, is the ability to ramp up production of these neutralizing antibodies again.  The immune system has a memory mechanism, by which once it has produced antibodies to a particular virus, it can remember and ramp up production of that same antibody if ever the virus comes back.

All that has been said here applies essentially the same for illness and for vaccination.  The bodily responses are not identical, but the basics here are the same.

The Dynamics of the Immune Response

How your body responds to a virus when you have been reinfected after you have developed an immunity therefore depends on several circumstances.

First, what are the remaining levels of neutralizing antibodies in your system?  If they are currently still high, the virus may never have a decent shot at colonizing your body a second time and the infection will rapidly die, likely without you even noticing it.  Since you have a bunch of antibodies in your system, while the infection is progressing inside you, you are less likely to be infectious as virus particles you expel will tend to be coated in antibodies.  So you could test positive for Covid, but not be a risk to anyone around you.

If your levels of neutralizing antibodies are lower, however, the virus might start successfully spreading throughout your body, up until the point where your body takes notice of it and decides to start activating the innate immune response and ramping up production of the antibodies it already knows how to produce.

How sick you get and how infectious you will be to others now depends on timing.  It becomes a race between the virus becoming established and the body ramping up production of the neutralizing antibodies.  Factors for how this will end up include how healthy your immune system is and how effective your antibodies are against the new viral invader; so the outcomes can range widely.

What I think is happening with Delta and the vaccines

I believe that the dramatically decreased reported effectiveness of the vaccines against the Delta variant are principally due to this dynamic and not principally due to the genetic drift between Delta and original Covid.  It has been shown that neutralizing antibodies produced against original Covid do not work quite as well against Delta as against the original--but I believe this translates into a decrease of vaccine effectiveness something like from 95% to 88%, not all the way down to 39%.

Instead, what I believe is happening is that immunized individuals are getting reinfected with Covid after their neutralizing antibodies have waned somewhat.  There is then a period of time in which the virus is able to colonize their bodies before immune memory kicks in.  This triggers both the emergence of symptoms (which are what get noticed) and rapid uptick of production of neutralizing antibodies.

This is why Israel has been seeing a large increase in infections, but not a correspondingly large increase in hospitalizations or deaths.  In fact, I believe the symptoms that are being reported in Israel as "symptomatic Covid" are primarily immune response symptoms, very similar to what the vaccinated experience on their second dose of the vaccine.

I think evidence for this theory is reflected in the different experience that the U.K. has been having with Delta and the vaccines.  They have been seeing an effectiveness against symptomatic Covid with Delta in the vaccinated more like the 88% range.  But the crucial difference here is that the U.K. pursued a strategy in which they significantly delayed the second dose of the vaccine.  Therefore, most of those fully vaccinated individuals in the U.K. have not had the second dose until fairly recently.  Therefore their levels of neutralizing antibodies are still rather high, and the Delta variant is thus dealing with individuals who do not need a ramp-up time to fight it off.

What does this mean for infectiousness?

Does this mean that Covid is going to be able to spread well among people who were vaccinated back in December / January?  Is the time that the virus is able to reproduce in the body of people whose neutralizing antibody levels have waned somewhat enough time where it can then also spread to other people.

I think the answer to this question must be, yes, at least a bit.  I have a hard time thinking that this won't increase somewhat the ability of the virus to spread from vaccinated individuals.  However, that doesn't mean that I think that this will be a major factor.

The issue is, again, the timing.  While it has been shown that in some cases, Covid can incubate and spread as quickly as in a single day, this is not very common.  More commonly, a person becomes significantly infectious 3-5 days after becoming infected themselves.  Meanwhile, we have carefully watched antibody levels during the vaccine trials, and we see from that that whereas it takes the body a full 7-14 days to start making any antibodies at all after the first shot of vaccine, the second shot of the vaccine produces an almost immediate spike of antibody production--within a single day.

I therefore think that it is likely that in the large majority of cases, a vaccinated individual with lower levels of antibodies will begin producing antibodies and thus become mostly non-infectious before the virus gets a chance to truly blossom.  Presence of symptomatic Covid in vaccinated individuals is therefore usually a sign of delayed but operational immunity, and not necessarily a danger of infectiousness.